High-Dimensional Multi-omic Mapping of Post-Mortem Human Brain Using Iterative Indirect Immunofluorescence Imaging on Xenium-Processed Tissues
- 1Columbia University Irving Medical Center
Abstract
Spatial transcriptomics approaches provide crucial insights into gene expression distribution within intact tissue architecture, but they encounter limitations in detecting morphologically complex cell types, assessing their spatial associations with pathology, and accurately annotating cell types using RNA data alone. Therefore, we developed a robust post-processing workflow integrating Xenium spatial technology with iterative indirect immunofluorescence imaging (4i) on formalin-fixed paraffin-embedded (FFPE) human brain tissue. The post-Xenium 4i protocol presented here allows multi-omic tissue mapping, enabling deeper investigation of pathological microenvironments defined by the spatial distribution of neuropathological hallmarks and enrichment of specific cell populations. We applied this workflow on calcarine cortex tissue sections where cerebral amyloid angiopathy (CAA) burden is present, in addition to amyloid plaques and tau pathology, generating a 15-plex image that captures the complexity of the pathological microenvironment.
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BibTeX
@misc{karaahmet2026highdimensional,
title = {{High-Dimensional Multi-omic Mapping of Post-Mortem Human Brain Using Iterative Indirect Immunofluorescence Imaging on Xenium-Processed Tissues}},
author = {B. Karaahmet and T. Lama and A. Wang and W. Cao and V. Menon and H.-U. Klein and D. A. Bennett and P. De Jager and Y. Zhang and M. Taga},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.751033},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.751033v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - High-Dimensional Multi-omic Mapping of Post-Mortem Human Brain Using Iterative Indirect Immunofluorescence Imaging on Xenium-Processed Tissues
AU - B. Karaahmet
AU - T. Lama
AU - A. Wang
AU - W. Cao
AU - V. Menon
AU - H.-U. Klein
AU - D. A. Bennett
AU - P. De Jager
AU - Y. Zhang
AU - M. Taga
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.751033
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.751033v1
AB - Spatial transcriptomics approaches provide crucial insights into gene expression distribution within intact tissue architecture, but they encounter limitations in detecting morphologically complex cell types, assessing their spatial associations with pathology, and accurately annotating cell types using RNA data alone. Therefore, we developed a robust post-processing workflow integrating Xenium spatial technology with iterative indirect immunofluorescence imaging (4i) on formalin-fixed paraffin-embedded (FFPE) human brain tissue. The post-Xenium 4i protocol presented here allows multi-omic tissue mapping, enabling deeper investigation of pathological microenvironments defined by the spatial distribution of neuropathological hallmarks and enrichment of specific cell populations. We applied this workflow on calcarine cortex tissue sections where cerebral amyloid angiopathy (CAA) burden is present, in addition to amyloid plaques and tau pathology, generating a 15-plex image that captures the complexity of the pathological microenvironment.
ER -